Myelodysplastic Syndromes Clinical Trial
Official title:
A Phase I/II Study of LBH589 Plus Decitabine for Patients Age ≥ 60 Years With High Risk MDS or AML
This study is designed to evaluate the combination of LBH589 and decitabine in patients age ≥ 60 years with high risk Myelodysplastic Syndrome (IPSS Int-2 or High) or Acute Myeloid Leukemia.
Status | Active, not recruiting |
Enrollment | 51 |
Est. completion date | September 2015 |
Est. primary completion date | July 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 60 Years and older |
Eligibility |
Inclusion Criteria: - AML (except t(15;17), inv(16) or t(8;21) and variants) or high risk MDS (IPSS Int-2 or High) diagnosed according to WHO criteria (see Appendix 1) - Age = 60 years old - Not a candidate for allogeneic stem cell transplantation within next 12 weeks - Ability to provide written informed consent, obtained prior to participation in the study and any related procedures being performed - Patients must meet the following laboratory criteria: - Serum albumin = 3 g/dL - AST/SGOT and ALT/SGPT = 2.5 x upper limit of normal (ULN) ) or = 5.0 x ULN if the transaminase elevation is due to leukemic involvement - Serum bilirubin = 1.5 x ULN - Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 ml/min - Serum potassium = LLN - Serum phosphorus = LLN - Serum total calcium (corrected for serum albumin) or serum ionized calcium = LLN - Serum magnesium = LLN, TSH and free T4 within normal limits (WNL) (patients may be on thyroid hormone replacement) - Baseline MUGA or ECHO must demonstrate LVEF = the lower limit of the institutional normal. - ECOG Performance Status of = 2 Exclusion Criteria: - Prior treatment for MDS / AML with HDAC inhibitor or hypomethylating agent (e.g., Decitabine, azacitadine etc.) - Active CNS involvement with MDS/AML - Impaired cardiac function including any one of the following: - Screening ECG with a QTc > 450 msec confirmed by central laboratory prior to enrollment to the study - Patients with congenital long QT syndrome - History of sustained ventricular tachycardia - Any history of ventricular fibrillation or torsades de pointes - Bradycardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate = 50 beats per minute are eligible. - Patients with a myocardial infarction or unstable angina within 6 months of study entry - Congestive heart failure (NY Heart Association class III or IV) - Right bundle branch block and left anterior hemiblock (bifasicular block) - Uncontrolled hypertension - Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 2-1) - Patients with unresolved diarrhea > CTCAE grade 1 - Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral LBH589 - Other concurrent severe and/or uncontrolled medical conditions - Patients who have received chemotherapy or any investigational drug < 2 weeks or hydroxyurea < 48 hours prior to starting study drug or who have not recovered from side effects of such therapy. - Concomitant use of any anti-cancer therapy or radiation therapy - Male patients whose sexual partners are WOCBP not using effective birth control - Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required - Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent - Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first LBH589 treatment - Patients who have received targeted agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies - Patients who have undergone major surgery = 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy. |
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
United States | Washington University | St. Louis | Missouri |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine |
United States,
Cashen, A., G. J. Schiller, et al. (2006). Phase II Study of Low-Dose Decitabine for the Front-Line Treatment of Older Patients with Acute Myeloid Leukemia (AML). ASH Annual Meeting Abstracts 108(11): 1984.
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Phase I: To determine the maximum tolerated dose and dose limiting toxicity of LBH589 when given in combination with decitabine in patients age = 60 years with high risk MDS or AML. | Approximately 3.5 years total for MTD and approximately 28 days for the DLT | Yes | |
Primary | Phase II: To determine the rate of morphologic complete remission (CR) of LBH589 plus decitabine in patients age = 60 years with high risk MDS or AML. | Approximately 12 months | No | |
Secondary | To determine the rates of cytogenetic complete remission (CRc) morphologic complete remission with incomplete count recovery (CRi), overall response rate (CR+ CRi) and hematologic improvement. | Approximately 12 months | No | |
Secondary | To measure changes in quality of life scores, the FACT-Leu and FACT-Leu Trial Outcome Index (TOI) in patients treated with LBH589 plus decitabine. | Up to approximately 1 year after start of treatment | No | |
Secondary | To determine the time to response, remission duration, progression-free survival, event-free survival and overall survival of patients treated with LBH589 plus decitabine. | Length of study | No | |
Secondary | To determine the frequency of adverse events by grade and attribution | Up to approximately 13 months after start of treatment | Yes |
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